COAGUIATION, FIBRINLYSIS AND KALLIKREIN ACTIVATION IN SEVERE INFECTION AND SEPSIS : RELATION TO OUTCOME

1987 ◽  
Author(s):  
M Blamback ◽  
F Hesselvik ◽  
B Brodin ◽  
R Maller ◽  
R Gaffney
Keyword(s):  
Septic Shock ◽  
Platelet Count ◽  
Organ Failure ◽  
Protein C ◽  
Severe Infection ◽  
Plasminogen Activator Inhibitor ◽  
Progressive Increase ◽  
Endothelial Damage ◽  
Multiple Organ ◽  
Group I

Fatal multiple organ failure following severe infection may be related to early activation of protease cascade systems. The study aimed to relate changes in the below mentioned components to shock and outcome. Of 53 patients with severe infection, 30 did not develop shock (group I); 12 survived septic shock (groupII); and 11 died from organ failure after septic shock (groupIII). No patient had overt DIC. During the first 3 days after admission, blood was sampled daily for assay of: platelet count, fibrinogen, prothrombin complex, F XII, F VIIIiC, vWF:Ag, F VII, F V, anti thrombin, protein C, plasminogen, antiplasmin, plasminogen activator inhibitor (PAi), X-oligcmers, D-dimers, prekalli-krein, functional kallikrein inhibition (fKl), and fibronectin, by chramogenic substrate and inmunochemical techniques. The Proenzyme functioned, index (PFI) ves calculated combining the results of anti thrombin, plasminogen, antiplasmin, prekallikrein and fKL (Aasen, Acta Chir Scand 1985; 522: 211).Low (p<.001) initial values for F XII, prothrombin complex, F VII, antithrcmbin, protein C, prekallikrein, and fibronectin were seen in all groups. The shock groups (I-III) had in addition significant decreases in platelet count, antiplasmin, and plasminogen. Fibrinogen, F VIII :C, vWF:Ag, X-oligcmers, and D-dimers were significantly higher than normal in all groups. Shock patients had higher X-oligcmers and D-dimers, but lower fibrinogen than non-shock patients. PAi was within the normal range in survivors (I-II), but was elevated ten-fold and increased progressively over 3 days in the non-survivors. vWF:Ag showed a similar progressive increase in non^survivors; these two variables ware the best early indicators of non-survival. PFI was significantly lower in shock patients (II-III), but did not discern between survivors and non-survivors during days 1-3. The results indicate a marked activation of coagulation in patients with severe infection, with more fibrin formation and fibrinolysis in the shock groups. High vWF:Ag and PAi in non-survivors may indicate nmore endothelial damage, and potentially harmful fibrinolysis inhibition.

Fibrinolysis and Coagulation in Patients with Infectious Disease and Sepsis

1991 ◽  
Vol 65 (03) ◽  
pp. 291-295 ◽  
Author(s):  
J Philippé ◽  
F Offner ◽  
P J Declerck ◽  
G Leroux-Roels ◽  
D Vogelaers ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Plasminogen Activator ◽  
Protein C ◽  
Severe Infection ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
At Iii ◽  
C 30

SummarySepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 ± 9.4 versus 1.6 ± 1.5 ng/ml, p <0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 ± 390 ng/ml versus 120 ± 200 ng/ml, and 3.0 ± 3.6 IU/ml versus 1.0 ± 0.7 IU/ml, respectively, p <0.01). AT III was decreased in sepsis patients (58 ± 28% in sepsis versus 79 ± 26% in severe infectious disease, p <0.01) as was protein C (30 ± 18% versus 58 ± 27%, p <0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

scholarly journals Improving the therapy of generalized forms of Meningococcal infection in children using extracorporeal hemocorrection

2021 ◽  
Vol 20 (2) ◽  
pp. 49-56
Author(s):  
K. V. Markova ◽  
E. Yu. Skripchenko ◽  
K. V. Serednyakov ◽  
Yu. V. Lobzin ◽  
N. V. Skripchenko ◽  
...  
Keyword(s):  
Septic Shock ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Multiple Organ ◽  
Meningococcal Infection ◽  
Basic Drug ◽  
Inflammatory Reactions ◽  
Clinical Center ◽  
Refractory Septic Shock ◽  
Group 2

Invasive meningococcal infection is a significant cause of death, reaching 80% in septic shock. The Pediatric Research and Clinical Center for Infectious Diseases (PRCCID) has developed an algorithm for the treatment of children with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome, which includes basic drug therapy with polymyxin hemoperfusion in combination with extended methods of extracorporeal hemocorrection.Purpose: to evaluate the effectiveness of extracorporeal hemocorrection operations in children with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome.Materials and research methods: to the intensive care unit of the PRCCID for the analyzed period 2006—2020 34 children were hospitalized with invasive meningococcal infection with refractory septic shock and multiple organ failure syndrome. Two groups were formed: Group 1 — children admitted to the PRCCID in the period 2014—2020 (n = 23), who underwent polymyxin hemoperfusion simultaneously with extended methods of extracorporeal hemocorrection, group 2 — children hospitalized in 2006—201 3 (n = 1 1), methods of extracorporeal hemocorrection were not performed. The Mann-Whitney U-test and ANOVA were used to evaluate the results.Results and discussion: the use of extracorporeal hemocorrection operations in the complex therapy of invasive forms of meningococcal infection with refractory septic shock and multiple organ failure syndrome in children provides stabilization of central hemodynamics, reduces clinical and laboratory inflammatory reactions, helps to reduce the dose of vasopressor drugs and parameters of respiratory support, and also increases patient survival rate by 82.6%.

Impact of Age on Septic Shock and Multiple Organ Failure

2018 ◽  
Vol 227 (4) ◽  
pp. e113-e114
Author(s):  
Norma M. Smalls ◽  
Maria F. Nunez ◽  
Gezzer Ortega ◽  
Delaram J. Taghipour
Keyword(s):  
Septic Shock ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Multiple Organ

Septic Shock, Multiple Organ Failure, and Disseminated Intravascular Coagulation

CHEST Journal ◽  
1992 ◽  
Vol 101 (3) ◽  
pp. 816-823 ◽  
Author(s):  
Francois Fourrier ◽  
Claude Chopin ◽  
Jenny Goudemand ◽  
Sylvie Hendrycx ◽  
Claudine Caron ◽  
...  
Keyword(s):  
Septic Shock ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Disseminated Intravascular Coagulation ◽  
Multiple Organ ◽  
Intravascular Coagulation

Biological Rational for the Use of Heparin in Septic Shock: Translational Data from the Halo Pilot RCT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2336-2336
Author(s):  
Brett L. Houston ◽  
Dhruva J. Dwivedi ◽  
Peter Grin ◽  
Michelle Kwong ◽  
Enrico Rullo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Lysis Time ◽  
Activator Inhibitor ◽  
Clot Lysis Time

Abstract BACKGROUND: Sepsis is a leading cause of mortality among critically ill patients and is associated with both systemic inflammation and up-regulation of coagulation. In the translational sub-study of the HALO (Heparin AnticoaguLation to improve Outcomes in septic shock) pilot trial, we evaluated the mechanisms by which unfractionated heparin (UFH) may reduce inflammation and coagulation in patients with septic shock. METHODS: In this multicenter pilot randomized trial of 69 patients diagnosed with septic shock, we evaluated the feasibility of administering therapeutic dose intravenous UFH (18 IU/kg/hr) compared to thromboprophylactic subcutaneous dalteparin (5000 IU daily). Blood samples were collected on days 1 (baseline prior to study infusion), 2, 3, 5, and 7. We evaluated coagulation using assays for protein C, activated protein C, thrombin-antithrombin (TAT), thrombin generation, clot lysis, plasminogen activator inhibitor-1 (PAI-1) and cell-free DNA (cf-DNA). Systematic inflammation was evaluated by measuring inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, and IL-17). RESULTS: The mean age of the study population was 61 years, of whom 43% were male. Thirty two patients (46%) were randomized to receive unfractionated heparin while 37 (54%) received dalteparin. The baseline mean aggregate Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 ± 7.8, and Multiple Organ Dysfunction Score (MODS) 5.6 ± 2.38. Baseline laboratory testing (coagulation assays and inflammatory cytokines) was not statistically different between UFH vs. LMWH treated patients. On day 2, the median clot lysis time in UFH-treated patients compared to those receiving dalteparin was significantly decreased [6630 (IQR 0 - 14156) seconds vs. 9615 (IQR 8209 - 11018) seconds; p = 0.008] (Figure 1). UFH administration was associated with increased protein C levels [66.4% of normal (IQR 9.9 - 122.9) vs. 41.1% of normal (IQR 4.8 - 77.4); p = 0.02], and reduced thrombin generation of 0 (IQR 0 - 1725) units/min vs. 3393 (IQR 0 - 8519) units/min; p<0.001]. On day 2, we observed no differences between thrombin-antithrombin complex (TAT), activated protein C, plasminogen activator inhibitor-1 (PAI-1) or cell-free DNA (cf-DNA). Similarly, there were no differences between treatment groups in inflammatory markers, including IL-6, IL-8, IL-10 or IL-17. Analysis thus far is limited to samples collected on days 1 and 2; day 3-7 analyses are ongoing. CONCLUSION: In patients diagnosed with septic shock, IV UFH reduces thrombin generation, shortens clot lysis time and improves endogenous protein C levels compared to dalteparin administered for thromboprophylaxis. Analyses for samples obtained on days 3, 5 and 7 are ongoing. These preliminary data provide a biologic rational for the use of heparin in sepsis. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Disclosures No relevant conflicts of interest to declare.

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